1 of 46

PHYS 423�Applications of Biophysics

CCNY

2025.08.26

https://pdb101.rcsb.org/motm/motm-about

2 of 46

About Me

  • Lived in Michigan, California, Kentucky and Pennsylvania
  • B.S. in Biology and B.A. in Chemistry from the University of North Carolina
  • PhD Candidate at Weill Cornell Medical College in the Tri-Institutional PhD Program in Chemical Biology
  • Studying structure-based, computer-aided drug discovery
  • About to defend my PhD (Sep 19th)!

​

https://apayne97.github.io/

​

2

3 of 46

Class Structure

3 Sections:

  1. Foundations of biology, chemistry, biochemistry, and statistical mechanics
  2. Review of key protein classes and mechanisms
  3. Applications – Drug Discovery, Machine Learning Approaches, and Protein Design

3

4 of 46

Syllabus and Grading

​

4

5 of 46

Main Assignments – Flash Talk (9/30)

  • 1 slide, 2-3 minute talk
  • Slide should be sent before midnight on 9/29
    • If you send earlier, I will give you suggestions and you can resubmit.
  • The Goal:
    • To make sure you have the correct protein; have found a PDB structure and at least one good review so you can get started.
    • To know the big picture
      • The kinds of organisms contain your protein. (e.g. Plants; all aerobic organisms; …
      • Where your protein is located. (e.g. which membrane (nerve, chloroplast ...)
      • What your protein does for the cell. (How it fits into cell function)
      • Does your protein store energy or use energy?
  • More guidelines will be added soon

5

6 of 46

Main Assignments – Paper

  • At least 10 pages of a review on a particular protein
    • Abstract
    • Introduction
    • Structure
    • Function
    • Some particular sub-topic about the protein that you find interesting
  • Due the last day of class (12/11)

​

6

7 of 46

Main Assignments – Final Presentation

  • ~20 min presentation on your protein that reviews the main ideas you discuss in your paper

7

8 of 46

Break

8

9 of 46

Intro to Molecular Biophysics

Biology

Chemistry

Physics

9

10 of 46

Physical Laws are Really Useful

10

11 of 46

“All models are wrong, but some are useful.” �George E. P. Box

11

12 of 46

The problem with reductionism in biology

Recognizing when your model is relevant and useful is key

12

13 of 46

Biology is messy

13

14 of 46

Biology spans broad time and length scales

14

15 of 46

Small, molecular changes can have huge consequences:�Sickle Cell Anemia

15

16 of 46

Small, molecular changes can have huge consequences�Sickle Cell Anemia example

16

17 of 46

The goal of biophysics is to develop models that help us understand and predict biology

17

18 of 46

The molecular world is a chaotic system

18

19 of 46

Statistical mechanics describes how the molecular world works

  • Entropy
  • Energetic states
  • Boltzmann distribution
  • 2-state models

​

​

 

 

19

20 of 46

Nernst Potential Example

20

21 of 46

Nernst Potential Example

21

22 of 46

Nernst Potential Example

22

23 of 46

Nernst Potential Example

 

23

24 of 46

Nernst Potential Example

 

24

25 of 46

Break

25

26 of 46

WHAT IS LIFE?

26

27 of 46

The theory of evolution by natural selection

27

28 of 46

The theory of evolution by natural selection

28

29 of 46

Evolution results in some unexpected things!

29

30 of 46

Life at the cellular level

30

31 of 46

31

32 of 46

32

33 of 46

What is a cell?

33

34 of 46

Most cellular tasks are performed by biophysical machines!

  • Metabolism – extracting energy from the environment and building the chemical building blocks of life
  • Signaling – responding to cellular stimuli
  • Homeostasis – transporting molecules between cell compartments and into / out of the cells

We will also see how multicellular tasks, such as muscle contraction and neuronal signaling, evolved from these basic ones

34

35 of 46

Most biophysical machines are proteins

Cell signaling

Immune response

Oxygen transport

Energy production

Energy production

35

36 of 46

What are proteins?

36

37 of 46

What are proteins?

37

38 of 46

How are proteins?

  • Atomic forces
  • Interactions between parts of the protein
  • Packing (nature abhors a vacuum)
  • Electrostatics (amongst charges & dipoles)
  • Interaction with water
  • Solvation energy
  • Hydrophobicity

38

39 of 46

Break

39

40 of 46

DNA 🡪 RNA 🡪 Protein

  • not all dna codes for protein
  • some genes are present in multiple copies
  • transcriptome – what genes are transcribed to RNA
  • proteome – what proteins have been synthesized

​

40

41 of 46

Genome Size

41

42 of 46

Purpose of Genomics

  • Establish web based archive and search engines
  • Assemble physical maps of genome
  • Identify and order expressed sequences
  • Identify function of expressed genes
  • Compile atlas of gene expression
  • Compile functional data connected to each gene (biochemistry & phenotype)
  • Characterize diversity (SNP)
  • Compare with other genomes

​

42

43 of 46

Some Key Tools for Researching Proteins

  • Starting points
    • Wikipedia
    • LLMs (Claude, ChatGPT) – but make them find real sources!!
    • Google Scholar
  • Main protein and gene databases
    • BLAST – for finding proteins and genes like one you’re interested in
    • Uniprot – all protein information
    • Protein Data Bank – experimental structures
    • InterPro – for analyzing protein families and different classification methods
  • For visualization
    • PyMol
    • Chimera
  • For studying protein : drug interactions
    • chembl
    • DrugBank

43

44 of 46

Applications of Biophysics

  • Understanding molecular basis of biological phenomenon
  • Modulating function through chemical biology and drug discovery
  • Creating new tools for solving problems with protein design

44

45 of 46

Protein Analysis Via Pymol

  • 1A3N - DEOXY HUMAN HEMOGLOBIN
  • 6BB5 - Human Oxy-Hemoglobin
  • 7JY1 - Structure of HbA with compound 19

​

https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c01518

​

45

46 of 46

Housekeeping

  • Next class we will discuss chemistry foundations
  • Slack
  • Google Forms link

​

46